IL (Interleukin)-18 was originally described as IFN-γ-inducing factor because it was able to augment the production of IFN-γ from T cells and NK cells. As part of the IL-1 cytokine family, IL-18 is a multi-functional component of both the innate and the acquired immune response. Under various conditions the IL-18R1 and IL-18RAP (IL-18 Receptor Accessory Protein) are expressed on a variety of immune cells including NK cells, macrophages, neutrophils, B cells, and fully differentiated Th1 cells. IL-18 has been shown to work in synergy with other cytokines, including IL-12 and IL-4 and has been broadly implicated in autoimmune and inflammatory diseases as well as chronic allergic rhinitis and asthma. In the periphery, IL-18 is known to exert an influence on numerous and diverse T cell processes. It increases Fas ligand-mediated cytotoxicity on T cells and stimulates the development of CD8 effector T cells. IL-18 also promotes chemotaxis of T cells. Furthermore, IL-18 drives CD4 T cell effector responses; inducing IFN-γ production by Th1 cells and promoting production of IL-4, IL-5 and IL-13 in Th2 cells. IL-18 can also enhance Th2 responses (with IL-2) and is indispensable for Th17 responses. Transgenic overexpression of IL-18 h ad dramatic effects on the immune system, however, these studies did not focus on the effects on early thymocytes, perhaps due to the important role for this cytokine in Th1 and Th2 differentiation that has kept the spotlight on peripheral immune cell mechanisms. Although the immunomodulatory functions of IL-18 are relatively well defined, its potential role in hematopoiesis has not been investigated. Previous studies have demonstrated thymic expression of IL-18 and this cytokine has been shown to promote the differentiation of fetal DN thymocytes to thymic-derived dendritic cells. Furthermore, thymocyte stimulation with IL-18 can elicit production of Th1 and Th2 cytokines in the presence of IL-12 and IL-2, respectively.